The present invention relates in general to mass spectrometers, and in particular to laser desorption and ionization mass spectrometers (“LDI-MS”).
In the field of analytical chemistry, a technique that has demonstrated impressive development and popularity during the past decades involves the use of a Time-of-Flight Mass Spectrometer (“TOF-MS”). A TOF-MS generally comprises an ion source, an ion optic assembly, a flight tube (free flight region) and an ion detector. More generally the TOF-MS can be divided into ion source, mass analyzer, and detector systems.
The ion source in an LDI/TOF-MS includes a probe element, on which the sample is presented, and a laser, which directs pulses of laser light at the sample, desorbing analyte molecules from the probe surface and ionizing them.
The ion optic assembly, a sub-assembly of a TOF-MS, focuses and accelerates ions from the ion source before they enter the free flight region of the TOF-MS. For example, the ion optic assembly of a TOF-MS may be realized with three electrodes: (1) A source element (also called a repeller lens or sample plate); (2) an extraction lens element and (3) an acceleration lens element. Sometimes a fourth electrode is placed between the extraction lens and the acceleration electrode. In most LDI-MS instruments the source element comprises means for engaging a probe, such as pins that mate with holes in the probe, or a groove into which the probe is slid. In this way the sample is connected to the source element. In some instruments conducting grids are used in the apertures of the some or all of the lenses to limit the penetration of electric fields through these apertures from neighboring high field regions. For example, a grid across the aperture of the extraction element might be used to prevent penetration of the field between the extraction and acceleration elements into the space between the extraction and the source elements. While grids help to control the electric field between the extraction lens and the source they can also degrade the performance of the ion optics because ion can collide with grids or the small apertures in the grids can act as focusing elements themselves.
Modern LDI/TOF-MS instruments use pulsed ion extraction (PIE) to improve the resolution of the mass spectrometer. In pulsed extraction, independent potentials can be placed on the source and extraction lens to create an appropriate electric field between the plates before laser desorption/ionization. In some applications, the source and extraction elements are initially held at specific potentials so as to create an essentially zero field at or near the surface of the source. In some cases, it may be desirable to create an initial field at the surface of the source that retards or accelerates ions generated from the sample. In any case, a laser pulse desorbs and ionizes analyte molecules from the source, creating a plume of ions between the source and the extractor. At a predetermined time interval after ionization, predetermined voltages, an extraction pulse, are applied to the source and the extraction elements to create an accelerating field that propels ions of the appropriate charge through the aperture in the extraction lens and into the following optics where the ions are generally focused and accelerated before entering the free flight region. (See, e.g., Weinberger et al., Time-of-flight Mass Spectrometry, Encyclopedia of Analytical Chemistry R. A. Meyers (Ed.) pp. 11915-11984 John Wiley & Sons Ltd, Chichester, 2000.)
In current LDI/TOF-MS systems, a voltage source is typically required for each voltage difference between two ion optic elements. For example, in a system with pulsed ion extraction, voltage sources are typically required to 1) set the voltage of the ion source relative to the acceleration element, 2) set the DC voltage of the extraction element relative to the ion source, and 3) generate a pulse that is capacitively coupled to the extraction element to generate the extraction field. While separate voltage sources for each of these provides full control of the voltages of the ion optic elements, it also adds to the expense of the instrument.
There is a growing need to use mass spectrometers as assay devices. To be useful in this way mass spectrometers need to be sensitive and low in cost. Sensitivity requires the ability to detect as many ions as possible that are desorbed from the sample plate. To achieve this, appropriate ion optics and voltage sources are required. The cost of a mass spectrometer can be reduced by eliminating unnecessary elements and replacing expensive elements with low-cost versions.
It is an object of this invention to provide a low cost mass spectrometer without compromising the high sensitivity.